CA3039010A1 - Bacterial minicells for delivering nucleic acid adjuvants and methods of using the same - Google Patents
Bacterial minicells for delivering nucleic acid adjuvants and methods of using the same Download PDFInfo
- Publication number
- CA3039010A1 CA3039010A1 CA3039010A CA3039010A CA3039010A1 CA 3039010 A1 CA3039010 A1 CA 3039010A1 CA 3039010 A CA3039010 A CA 3039010A CA 3039010 A CA3039010 A CA 3039010A CA 3039010 A1 CA3039010 A1 CA 3039010A1
- Authority
- CA
- Canada
- Prior art keywords
- nucleic acid
- minicell
- cell
- minicells
- acid adjuvant
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 102000039446 nucleic acids Human genes 0.000 title claims abstract description 248
- 108020004707 nucleic acids Proteins 0.000 title claims abstract description 248
- 150000007523 nucleic acids Chemical class 0.000 title claims abstract description 243
- 239000002671 adjuvant Substances 0.000 title claims abstract description 151
- 238000000034 method Methods 0.000 title claims abstract description 68
- 230000001580 bacterial effect Effects 0.000 title claims description 41
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 59
- 201000010099 disease Diseases 0.000 claims abstract description 42
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 42
- 238000011282 treatment Methods 0.000 claims abstract description 39
- 201000011510 cancer Diseases 0.000 claims abstract description 36
- 239000013612 plasmid Substances 0.000 claims abstract description 28
- 230000028993 immune response Effects 0.000 claims abstract description 19
- 210000004027 cell Anatomy 0.000 claims description 137
- 239000000203 mixture Substances 0.000 claims description 73
- 239000000556 agonist Substances 0.000 claims description 69
- 239000003814 drug Substances 0.000 claims description 52
- 239000003446 ligand Substances 0.000 claims description 37
- 210000002865 immune cell Anatomy 0.000 claims description 29
- 229940079593 drug Drugs 0.000 claims description 28
- 102000040430 polynucleotide Human genes 0.000 claims description 27
- 108091033319 polynucleotide Proteins 0.000 claims description 27
- 239000002157 polynucleotide Substances 0.000 claims description 27
- 210000004962 mammalian cell Anatomy 0.000 claims description 24
- 125000003729 nucleotide group Chemical group 0.000 claims description 21
- 102000005962 receptors Human genes 0.000 claims description 19
- 108020003175 receptors Proteins 0.000 claims description 19
- 239000002773 nucleotide Substances 0.000 claims description 18
- 208000015181 infectious disease Diseases 0.000 claims description 15
- 210000004443 dendritic cell Anatomy 0.000 claims description 13
- 238000004519 manufacturing process Methods 0.000 claims description 13
- 102000000844 Cell Surface Receptors Human genes 0.000 claims description 12
- 108010001857 Cell Surface Receptors Proteins 0.000 claims description 12
- 239000002158 endotoxin Substances 0.000 claims description 10
- 102100037435 Antiviral innate immune response receptor RIG-I Human genes 0.000 claims description 9
- 101000669402 Homo sapiens Toll-like receptor 7 Proteins 0.000 claims description 9
- 102100039390 Toll-like receptor 7 Human genes 0.000 claims description 9
- 238000001727 in vivo Methods 0.000 claims description 9
- 101000831496 Homo sapiens Toll-like receptor 3 Proteins 0.000 claims description 8
- 101000800483 Homo sapiens Toll-like receptor 8 Proteins 0.000 claims description 8
- 102100024324 Toll-like receptor 3 Human genes 0.000 claims description 8
- 102100033110 Toll-like receptor 8 Human genes 0.000 claims description 8
- 229920001282 polysaccharide Polymers 0.000 claims description 8
- 239000005017 polysaccharide Substances 0.000 claims description 8
- 108010014726 Interferon Type I Proteins 0.000 claims description 7
- 102000002227 Interferon Type I Human genes 0.000 claims description 7
- 102100027353 Interferon-induced helicase C domain-containing protein 1 Human genes 0.000 claims description 7
- 102100024064 Interferon-inducible protein AIM2 Human genes 0.000 claims description 7
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 7
- 108010060818 Toll-Like Receptor 9 Proteins 0.000 claims description 7
- 102100033117 Toll-like receptor 9 Human genes 0.000 claims description 7
- 229920006008 lipopolysaccharide Polymers 0.000 claims description 7
- 230000000242 pagocytic effect Effects 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 6
- 229940115272 polyinosinic:polycytidylic acid Drugs 0.000 claims description 6
- 230000003213 activating effect Effects 0.000 claims description 5
- 229960002751 imiquimod Drugs 0.000 claims description 5
- DOUYETYNHWVLEO-UHFFFAOYSA-N imiquimod Chemical compound C1=CC=CC2=C3N(CC(C)C)C=NC3=C(N)N=C21 DOUYETYNHWVLEO-UHFFFAOYSA-N 0.000 claims description 5
- 238000000338 in vitro Methods 0.000 claims description 5
- 210000002540 macrophage Anatomy 0.000 claims description 5
- 230000010837 receptor-mediated endocytosis Effects 0.000 claims description 5
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 4
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 4
- 239000012648 POLY-ICLC Substances 0.000 claims description 4
- 230000000840 anti-viral effect Effects 0.000 claims description 4
- 108700002563 poly ICLC Proteins 0.000 claims description 4
- 229940115270 poly iclc Drugs 0.000 claims description 4
- 230000001105 regulatory effect Effects 0.000 claims description 4
- 102100031256 Cyclic GMP-AMP synthase Human genes 0.000 claims description 3
- 101710118064 Cyclic GMP-AMP synthase Proteins 0.000 claims description 3
- 206010057249 Phagocytosis Diseases 0.000 claims description 3
- 230000000973 chemotherapeutic effect Effects 0.000 claims description 3
- 210000005260 human cell Anatomy 0.000 claims description 2
- 108060000255 AIM2 Proteins 0.000 claims 2
- 101710127675 Antiviral innate immune response receptor RIG-I Proteins 0.000 claims 2
- 102100039928 Gamma-interferon-inducible protein 16 Human genes 0.000 claims 2
- 101000960209 Homo sapiens Gamma-interferon-inducible protein 16 Proteins 0.000 claims 2
- 101001082073 Homo sapiens Interferon-induced helicase C domain-containing protein 1 Proteins 0.000 claims 2
- 229940046166 oligodeoxynucleotide Drugs 0.000 claims 2
- 230000001613 neoplastic effect Effects 0.000 abstract description 2
- 108020004414 DNA Proteins 0.000 description 33
- 239000013598 vector Substances 0.000 description 33
- 238000009472 formulation Methods 0.000 description 30
- 230000014509 gene expression Effects 0.000 description 28
- 108090000623 proteins and genes Proteins 0.000 description 28
- 102000004169 proteins and genes Human genes 0.000 description 22
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 19
- 108091034117 Oligonucleotide Proteins 0.000 description 17
- 102000014150 Interferons Human genes 0.000 description 14
- 108010050904 Interferons Proteins 0.000 description 14
- 101001034842 Homo sapiens Interferon-induced transmembrane protein 2 Proteins 0.000 description 13
- 102100040020 Interferon-induced transmembrane protein 2 Human genes 0.000 description 13
- 241000699670 Mus sp. Species 0.000 description 13
- 108090000765 processed proteins & peptides Proteins 0.000 description 13
- 229940124597 therapeutic agent Drugs 0.000 description 13
- 230000027455 binding Effects 0.000 description 12
- 239000012528 membrane Substances 0.000 description 12
- 230000001225 therapeutic effect Effects 0.000 description 12
- 230000000694 effects Effects 0.000 description 11
- 229920001184 polypeptide Polymers 0.000 description 11
- 102000004196 processed proteins & peptides Human genes 0.000 description 11
- 229940126585 therapeutic drug Drugs 0.000 description 11
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 10
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 10
- 230000000259 anti-tumor effect Effects 0.000 description 10
- 230000004048 modification Effects 0.000 description 10
- 238000012986 modification Methods 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 102000053602 DNA Human genes 0.000 description 9
- 230000000295 complement effect Effects 0.000 description 9
- 210000000805 cytoplasm Anatomy 0.000 description 9
- 229940047124 interferons Drugs 0.000 description 9
- 208000024891 symptom Diseases 0.000 description 9
- 102000004127 Cytokines Human genes 0.000 description 8
- 108090000695 Cytokines Proteins 0.000 description 8
- 230000006870 function Effects 0.000 description 8
- 101000952099 Homo sapiens Antiviral innate immune response receptor RIG-I Proteins 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 7
- 230000004913 activation Effects 0.000 description 7
- 230000035772 mutation Effects 0.000 description 7
- 210000004940 nucleus Anatomy 0.000 description 7
- 230000011664 signaling Effects 0.000 description 7
- 235000000346 sugar Nutrition 0.000 description 7
- 241000894006 Bacteria Species 0.000 description 6
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 6
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 6
- 102100040019 Interferon alpha-1/13 Human genes 0.000 description 6
- 108010076504 Protein Sorting Signals Proteins 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 239000005090 green fluorescent protein Substances 0.000 description 6
- 210000000987 immune system Anatomy 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 239000000523 sample Substances 0.000 description 6
- 230000028327 secretion Effects 0.000 description 6
- 229940046168 CpG oligodeoxynucleotide Drugs 0.000 description 5
- 241000588724 Escherichia coli Species 0.000 description 5
- 101000833614 Homo sapiens Interferon-inducible protein AIM2 Proteins 0.000 description 5
- 108010044240 IFIH1 Interferon-Induced Helicase Proteins 0.000 description 5
- 108020004459 Small interfering RNA Proteins 0.000 description 5
- 150000001413 amino acids Chemical class 0.000 description 5
- 230000009286 beneficial effect Effects 0.000 description 5
- 230000032823 cell division Effects 0.000 description 5
- 230000002068 genetic effect Effects 0.000 description 5
- 238000009396 hybridization Methods 0.000 description 5
- 229940079322 interferon Drugs 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 230000037361 pathway Effects 0.000 description 5
- 230000003285 pharmacodynamic effect Effects 0.000 description 5
- 239000002504 physiological saline solution Substances 0.000 description 5
- 230000008707 rearrangement Effects 0.000 description 5
- -1 ssRNA Proteins 0.000 description 5
- 238000013518 transcription Methods 0.000 description 5
- 230000035897 transcription Effects 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 229910019142 PO4 Inorganic materials 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- 239000000356 contaminant Substances 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 238000001085 differential centrifugation Methods 0.000 description 4
- 238000002296 dynamic light scattering Methods 0.000 description 4
- 230000012202 endocytosis Effects 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 238000010255 intramuscular injection Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 230000034701 macropinocytosis Effects 0.000 description 4
- 238000004806 packaging method and process Methods 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 4
- 239000010452 phosphate Substances 0.000 description 4
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 description 4
- 210000005134 plasmacytoid dendritic cell Anatomy 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 150000008163 sugars Chemical class 0.000 description 4
- 231100000331 toxic Toxicity 0.000 description 4
- 230000002588 toxic effect Effects 0.000 description 4
- 210000004881 tumor cell Anatomy 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 102000002689 Toll-like receptor Human genes 0.000 description 3
- 108020000411 Toll-like receptor Proteins 0.000 description 3
- 238000007792 addition Methods 0.000 description 3
- 125000003275 alpha amino acid group Chemical group 0.000 description 3
- 230000005907 cancer growth Effects 0.000 description 3
- 210000002421 cell wall Anatomy 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 230000001086 cytosolic effect Effects 0.000 description 3
- 239000002254 cytotoxic agent Substances 0.000 description 3
- 229940127089 cytotoxic agent Drugs 0.000 description 3
- 230000002354 daily effect Effects 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- 238000000432 density-gradient centrifugation Methods 0.000 description 3
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 3
- 230000002163 immunogen Effects 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 238000010253 intravenous injection Methods 0.000 description 3
- 230000003211 malignant effect Effects 0.000 description 3
- 210000001616 monocyte Anatomy 0.000 description 3
- 230000009871 nonspecific binding Effects 0.000 description 3
- 230000001717 pathogenic effect Effects 0.000 description 3
- 230000000770 proinflammatory effect Effects 0.000 description 3
- 230000001737 promoting effect Effects 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 230000006641 stabilisation Effects 0.000 description 3
- 238000011105 stabilization Methods 0.000 description 3
- 238000010254 subcutaneous injection Methods 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 230000004614 tumor growth Effects 0.000 description 3
- 239000012646 vaccine adjuvant Substances 0.000 description 3
- SLURUCSFDHKXFR-WWMWMSKMSA-N (7s,9s)-7-[[(1s,3r,4as,9s,9ar,10as)-9-methoxy-1-methyl-3,4,4a,6,7,9,9a,10a-octahydro-1h-pyrano[1,2][1,3]oxazolo[3,4-b][1,4]oxazin-3-yl]oxy]-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione Chemical compound O=C1C2=CC=CC(OC)=C2C(=O)C(C(O)=C23)=C1C(O)=C3C[C@@](O)(C(=O)CO)C[C@@H]2O[C@H]1C[C@@H]2N3CCO[C@H](OC)[C@H]3O[C@@H]2[C@H](C)O1 SLURUCSFDHKXFR-WWMWMSKMSA-N 0.000 description 2
- XRILCFTWUCUKJR-INFSMZHSSA-N 2'-3'-cGAMP Chemical compound C([C@H]([C@H]1O)O2)OP(O)(=O)O[C@H]3[C@@H](O)[C@H](N4C5=NC=NC(N)=C5N=C4)O[C@@H]3COP(O)(=O)O[C@H]1[C@@H]2N1C=NC2=C1NC(N)=NC2=O XRILCFTWUCUKJR-INFSMZHSSA-N 0.000 description 2
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- 241000242764 Aequorea victoria Species 0.000 description 2
- 108020000946 Bacterial DNA Proteins 0.000 description 2
- 208000003170 Bronchiolo-Alveolar Adenocarcinoma Diseases 0.000 description 2
- 241000192125 Firmicutes Species 0.000 description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101001054334 Homo sapiens Interferon beta Proteins 0.000 description 2
- 101001011382 Homo sapiens Interferon regulatory factor 3 Proteins 0.000 description 2
- 101000643024 Homo sapiens Stimulator of interferon genes protein Proteins 0.000 description 2
- 101000637726 Homo sapiens Toll/interleukin-1 receptor domain-containing adapter protein Proteins 0.000 description 2
- 102100026720 Interferon beta Human genes 0.000 description 2
- 102100029843 Interferon regulatory factor 3 Human genes 0.000 description 2
- 102000043136 MAP kinase family Human genes 0.000 description 2
- 108091054455 MAP kinase family Proteins 0.000 description 2
- 108060004795 Methyltransferase Proteins 0.000 description 2
- 108091028664 Ribonucleotide Proteins 0.000 description 2
- 241001180364 Spirochaetes Species 0.000 description 2
- 102100032120 Toll/interleukin-1 receptor domain-containing adapter protein Human genes 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- 230000030741 antigen processing and presentation Effects 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 230000003190 augmentative effect Effects 0.000 description 2
- 230000004993 binary fission Effects 0.000 description 2
- 208000002352 blister Diseases 0.000 description 2
- 230000009702 cancer cell proliferation Effects 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 229940044683 chemotherapy drug Drugs 0.000 description 2
- 210000000349 chromosome Anatomy 0.000 description 2
- 230000024321 chromosome segregation Effects 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 238000009295 crossflow filtration Methods 0.000 description 2
- ZOOGRGPOEVQQDX-UHFFFAOYSA-N cyclic GMP Natural products O1C2COP(O)(=O)OC2C(O)C1N1C=NC2=C1NC(N)=NC2=O ZOOGRGPOEVQQDX-UHFFFAOYSA-N 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 210000000172 cytosol Anatomy 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000001493 electron microscopy Methods 0.000 description 2
- 230000004651 endocytosis pathway Effects 0.000 description 2
- 210000001163 endosome Anatomy 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 102000037865 fusion proteins Human genes 0.000 description 2
- 108020001507 fusion proteins Proteins 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000010249 in-situ analysis Methods 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 210000005007 innate immune system Anatomy 0.000 description 2
- 239000007927 intramuscular injection Substances 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 210000004901 leucine-rich repeat Anatomy 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 125000005647 linker group Chemical group 0.000 description 2
- GZQKNULLWNGMCW-PWQABINMSA-N lipid A (E. coli) Chemical compound O1[C@H](CO)[C@@H](OP(O)(O)=O)[C@H](OC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCCCC)[C@@H](NC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCC)[C@@H]1OC[C@@H]1[C@@H](O)[C@H](OC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](NC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](OP(O)(O)=O)O1 GZQKNULLWNGMCW-PWQABINMSA-N 0.000 description 2
- 230000004807 localization Effects 0.000 description 2
- 230000002132 lysosomal effect Effects 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 229910021645 metal ion Inorganic materials 0.000 description 2
- 230000001394 metastastic effect Effects 0.000 description 2
- 206010061289 metastatic neoplasm Diseases 0.000 description 2
- 108091070501 miRNA Proteins 0.000 description 2
- 239000002679 microRNA Substances 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 2
- 150000004713 phosphodiesters Chemical class 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000007115 recruitment Effects 0.000 description 2
- 229950010550 resiquimod Drugs 0.000 description 2
- BXNMTOQRYBFHNZ-UHFFFAOYSA-N resiquimod Chemical compound C1=CC=CC2=C(N(C(COCC)=N3)CC(C)(C)O)C3=C(N)N=C21 BXNMTOQRYBFHNZ-UHFFFAOYSA-N 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 239000002336 ribonucleotide Substances 0.000 description 2
- 125000002652 ribonucleotide group Chemical class 0.000 description 2
- 238000005204 segregation Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 238000011269 treatment regimen Methods 0.000 description 2
- 229940124931 vaccine adjuvant Drugs 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- ASJSAQIRZKANQN-CRCLSJGQSA-N 2-deoxy-D-ribose Chemical compound OC[C@@H](O)[C@@H](O)CC=O ASJSAQIRZKANQN-CRCLSJGQSA-N 0.000 description 1
- RHKWIGHJGOEUSM-UHFFFAOYSA-N 3h-imidazo[4,5-h]quinoline Chemical class C1=CN=C2C(N=CN3)=C3C=CC2=C1 RHKWIGHJGOEUSM-UHFFFAOYSA-N 0.000 description 1
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 1
- 241001114404 Acholeplasmatales Species 0.000 description 1
- 241000580482 Acidobacteria Species 0.000 description 1
- 241001156739 Actinobacteria <phylum> Species 0.000 description 1
- 241000203716 Actinomycetaceae Species 0.000 description 1
- 241000203809 Actinomycetales Species 0.000 description 1
- 241001114462 Anaeroplasmatales Species 0.000 description 1
- 102000006410 Apoproteins Human genes 0.000 description 1
- 108010083590 Apoproteins Proteins 0.000 description 1
- 241001142141 Aquificae <phylum> Species 0.000 description 1
- 241001112741 Bacillaceae Species 0.000 description 1
- 241000193833 Bacillales Species 0.000 description 1
- 241000304886 Bacilli Species 0.000 description 1
- 101100421923 Bacillus subtilis (strain 168) spo0J gene Proteins 0.000 description 1
- 108090000363 Bacterial Luciferases Proteins 0.000 description 1
- 241000605059 Bacteroidetes Species 0.000 description 1
- 206010004146 Basal cell carcinoma Diseases 0.000 description 1
- 241001430332 Bifidobacteriaceae Species 0.000 description 1
- 241001655328 Bifidobacteriales Species 0.000 description 1
- 241001474374 Blennius Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241001655314 Brevibacteriaceae Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 235000014653 Carica parviflora Nutrition 0.000 description 1
- 102000011727 Caspases Human genes 0.000 description 1
- 108010076667 Caspases Proteins 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 241000191368 Chlorobi Species 0.000 description 1
- 241001142109 Chloroflexi Species 0.000 description 1
- 241001143290 Chrysiogenetes <phylum> Species 0.000 description 1
- 241001112696 Clostridia Species 0.000 description 1
- 241001112695 Clostridiales Species 0.000 description 1
- 241000243321 Cnidaria Species 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 241001274613 Corvus frugilegus Species 0.000 description 1
- 241000186031 Corynebacteriaceae Species 0.000 description 1
- 241001655326 Corynebacteriales Species 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 241000192700 Cyanobacteria Species 0.000 description 1
- IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-N 0.000 description 1
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
- 108010041052 DNA Topoisomerase IV Proteins 0.000 description 1
- 230000004568 DNA-binding Effects 0.000 description 1
- 241001143296 Deferribacteres <phylum> Species 0.000 description 1
- CYCGRDQQIOGCKX-UHFFFAOYSA-N Dehydro-luciferin Natural products OC(=O)C1=CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 CYCGRDQQIOGCKX-UHFFFAOYSA-N 0.000 description 1
- 241000192095 Deinococcus-Thermus Species 0.000 description 1
- 241001135761 Deltaproteobacteria Species 0.000 description 1
- 241000970811 Dictyoglomi Species 0.000 description 1
- 241000353621 Eilat virus Species 0.000 description 1
- 241000588921 Enterobacteriaceae Species 0.000 description 1
- 241001609975 Enterococcaceae Species 0.000 description 1
- 241001114405 Entomoplasmatales Species 0.000 description 1
- 241001148568 Epsilonproteobacteria Species 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 108090000371 Esterases Proteins 0.000 description 1
- 108010023321 Factor VII Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 241000923108 Fibrobacteres Species 0.000 description 1
- BJGNCJDXODQBOB-UHFFFAOYSA-N Fivefly Luciferin Natural products OC(=O)C1CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 BJGNCJDXODQBOB-UHFFFAOYSA-N 0.000 description 1
- 241001279371 Frankiaceae Species 0.000 description 1
- 241001655320 Frankiales Species 0.000 description 1
- 241001453172 Fusobacteria Species 0.000 description 1
- 241001265526 Gemmatimonadetes <phylum> Species 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102100031153 Growth arrest and DNA damage-inducible protein GADD45 beta Human genes 0.000 description 1
- 241000520860 Halanaerobiales Species 0.000 description 1
- 241001496656 Haloplasmatales Species 0.000 description 1
- 101000851181 Homo sapiens Epidermal growth factor receptor Proteins 0.000 description 1
- 101001066164 Homo sapiens Growth arrest and DNA damage-inducible protein GADD45 beta Proteins 0.000 description 1
- 101001066878 Homo sapiens Polyribonucleotide nucleotidyltransferase 1, mitochondrial Proteins 0.000 description 1
- 101001082184 Homo sapiens Pyrin and HIN domain-containing protein 1 Proteins 0.000 description 1
- 101000595548 Homo sapiens TIR domain-containing adapter molecule 1 Proteins 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 102000006940 Interleukin-1 Receptor-Associated Kinases Human genes 0.000 description 1
- 108010072621 Interleukin-1 Receptor-Associated Kinases Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 241001468155 Lactobacillaceae Species 0.000 description 1
- 241001112724 Lactobacillales Species 0.000 description 1
- 241001387859 Lentisphaerae Species 0.000 description 1
- 241001609976 Leuconostocaceae Species 0.000 description 1
- 241001112727 Listeriaceae Species 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- DDWFXDSYGUXRAY-UHFFFAOYSA-N Luciferin Natural products CCc1c(C)c(CC2NC(=O)C(=C2C=C)C)[nH]c1Cc3[nH]c4C(=C5/NC(CC(=O)O)C(C)C5CC(=O)O)CC(=O)c4c3C DDWFXDSYGUXRAY-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 241001655327 Micrococcales Species 0.000 description 1
- 102100023727 Mitochondrial antiviral-signaling protein Human genes 0.000 description 1
- 101710142315 Mitochondrial antiviral-signaling protein Proteins 0.000 description 1
- 241001430197 Mollicutes Species 0.000 description 1
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 1
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 1
- 241000186360 Mycobacteriaceae Species 0.000 description 1
- 241000204003 Mycoplasmatales Species 0.000 description 1
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
- 241000121237 Nitrospirae Species 0.000 description 1
- 241001655308 Nocardiaceae Species 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- TTZMPOZCBFTTPR-UHFFFAOYSA-N O=P1OCO1 Chemical compound O=P1OCO1 TTZMPOZCBFTTPR-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091093037 Peptide nucleic acid Proteins 0.000 description 1
- 108700019535 Phosphoprotein Phosphatases Proteins 0.000 description 1
- 102000045595 Phosphoprotein Phosphatases Human genes 0.000 description 1
- 241001180199 Planctomycetes Species 0.000 description 1
- 108091036414 Polyinosinic:polycytidylic acid Proteins 0.000 description 1
- 102000002681 Polyribonucleotide nucleotidyltransferase Human genes 0.000 description 1
- 101710128017 Polyribonucleotide nucleotidyltransferase 1, mitochondrial Proteins 0.000 description 1
- 102100034410 Polyribonucleotide nucleotidyltransferase 1, mitochondrial Human genes 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 241000192142 Proteobacteria Species 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 102000005583 Pyrin Human genes 0.000 description 1
- 108010059278 Pyrin Proteins 0.000 description 1
- 102100027365 Pyrin and HIN domain-containing protein 1 Human genes 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 108010083644 Ribonucleases Proteins 0.000 description 1
- 102000006382 Ribonucleases Human genes 0.000 description 1
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
- 241000242583 Scyphozoa Species 0.000 description 1
- 102100038192 Serine/threonine-protein kinase TBK1 Human genes 0.000 description 1
- 101710106944 Serine/threonine-protein kinase TBK1 Proteins 0.000 description 1
- 238000002105 Southern blotting Methods 0.000 description 1
- 241000230565 Sphingobacteriia Species 0.000 description 1
- 241000295644 Staphylococcaceae Species 0.000 description 1
- 102100035533 Stimulator of interferon genes protein Human genes 0.000 description 1
- 241000194018 Streptococcaceae Species 0.000 description 1
- 241000390529 Synergistetes Species 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- 238000003917 TEM image Methods 0.000 description 1
- 102100036073 TIR domain-containing adapter molecule 1 Human genes 0.000 description 1
- 241000131694 Tenericutes Species 0.000 description 1
- 241000970807 Thermoanaerobacterales Species 0.000 description 1
- 241001143138 Thermodesulfobacteria <phylum> Species 0.000 description 1
- 241001143310 Thermotogae <phylum> Species 0.000 description 1
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 1
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical group O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 1
- 108020005202 Viral DNA Proteins 0.000 description 1
- 108010003533 Viral Envelope Proteins Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 102000011012 XC chemokine receptor 1 Human genes 0.000 description 1
- 108050001086 XC chemokine receptor 1 Proteins 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 208000009621 actinic keratosis Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000033289 adaptive immune response Effects 0.000 description 1
- 108091005764 adaptor proteins Proteins 0.000 description 1
- 102000035181 adaptor proteins Human genes 0.000 description 1
- 230000000240 adjuvant effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 230000004931 aggregating effect Effects 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
- 230000001668 ameliorated effect Effects 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 230000005975 antitumor immune response Effects 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 238000011717 athymic nude mouse Methods 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 208000035269 cancer or benign tumor Diseases 0.000 description 1
- 229940022399 cancer vaccine Drugs 0.000 description 1
- 238000009566 cancer vaccine Methods 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 239000002771 cell marker Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 108091092356 cellular DNA Proteins 0.000 description 1
- 210000003850 cellular structure Anatomy 0.000 description 1
- SQQXRXKYTKFFSM-UHFFFAOYSA-N chembl1992147 Chemical compound OC1=C(OC)C(OC)=CC=C1C1=C(C)C(C(O)=O)=NC(C=2N=C3C4=NC(C)(C)N=C4C(OC)=C(O)C3=CC=2)=C1N SQQXRXKYTKFFSM-UHFFFAOYSA-N 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000012866 crystallographic experiment Methods 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 238000011461 current therapy Methods 0.000 description 1
- 108091007930 cytoplasmic receptors Proteins 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 239000005547 deoxyribonucleotide Chemical class 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical class 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
- NAGJZTKCGNOGPW-UHFFFAOYSA-K dioxido-sulfanylidene-sulfido-$l^{5}-phosphane Chemical compound [O-]P([O-])([S-])=S NAGJZTKCGNOGPW-UHFFFAOYSA-K 0.000 description 1
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical class [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 229940125542 dual agonist Drugs 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 230000009881 electrostatic interaction Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000011013 endotoxin removal Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 238000009093 first-line therapy Methods 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 239000003228 hemolysin Substances 0.000 description 1
- 230000002607 hemopoietic effect Effects 0.000 description 1
- 102000045108 human EGFR Human genes 0.000 description 1
- 102000050022 human STING1 Human genes 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 1
- 229940124669 imidazoquinoline Drugs 0.000 description 1
- 238000001597 immobilized metal affinity chromatography Methods 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 230000007124 immune defense Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 230000009851 immunogenic response Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 238000011503 in vivo imaging Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 230000010468 interferon response Effects 0.000 description 1
- 102000014909 interleukin-1 receptor activity proteins Human genes 0.000 description 1
- 108040006732 interleukin-1 receptor activity proteins Proteins 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 230000002601 intratumoral effect Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 150000002605 large molecules Chemical class 0.000 description 1
- 108020001756 ligand binding domains Proteins 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 210000003712 lysosome Anatomy 0.000 description 1
- 230000001868 lysosomic effect Effects 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 108010082117 matrigel Proteins 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 1
- HSMRCPIZVMDSHN-UHFFFAOYSA-N methylaminomethylphosphonic acid Chemical compound CNCP(O)(O)=O HSMRCPIZVMDSHN-UHFFFAOYSA-N 0.000 description 1
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical compound CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 1
- 101150110189 minE gene Proteins 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 210000001700 mitochondrial membrane Anatomy 0.000 description 1
- 108091005601 modified peptides Proteins 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 1
- 101150035528 mukB gene Proteins 0.000 description 1
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 1
- 210000000581 natural killer T-cell Anatomy 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 230000009826 neoplastic cell growth Effects 0.000 description 1
- 230000000683 nonmetastatic effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 229960001972 panitumumab Drugs 0.000 description 1
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 150000008300 phosphoramidites Chemical group 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000008884 pinocytosis Effects 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 1
- 231100000683 possible toxicity Toxicity 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 229940021993 prophylactic vaccine Drugs 0.000 description 1
- 230000004850 protein–protein interaction Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000004017 serum-free culture medium Substances 0.000 description 1
- 229940126586 small molecule drug Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 230000004960 subcellular localization Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 229940021747 therapeutic vaccine Drugs 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 238000011100 viral filtration Methods 0.000 description 1
- 230000002618 waking effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 238000012447 xenograft mouse model Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/12—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria
- C07K16/1203—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-negative bacteria
- C07K16/1228—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-negative bacteria from Enterobacteriaceae (F), e.g. Citrobacter, Serratia, Proteus, Providencia, Morganella, Yersinia
- C07K16/1235—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-negative bacteria from Enterobacteriaceae (F), e.g. Citrobacter, Serratia, Proteus, Providencia, Morganella, Yersinia from Salmonella (G)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2863—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
- C12N15/1034—Isolating an individual clone by screening libraries
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/117—Nucleic acids having immunomodulatory properties, e.g. containing CpG-motifs
-
- C—CHEMISTRY; METALLURGY
- C40—COMBINATORIAL TECHNOLOGY
- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B40/00—Libraries per se, e.g. arrays, mixtures
- C40B40/02—Libraries contained in or displayed by microorganisms, e.g. bacteria or animal cells; Libraries contained in or displayed by vectors, e.g. plasmids; Libraries containing only microorganisms or vectors
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/52—Bacterial cells; Fungal cells; Protozoal cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55561—CpG containing adjuvants; Oligonucleotide containing adjuvants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Biomedical Technology (AREA)
- Microbiology (AREA)
- Biophysics (AREA)
- Biotechnology (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Physics & Mathematics (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Plant Pathology (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Crystallography & Structural Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Cell Biology (AREA)
- Food Science & Technology (AREA)
- Pathology (AREA)
- Gastroenterology & Hepatology (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662405074P | 2016-10-06 | 2016-10-06 | |
| US62/405,074 | 2016-10-06 | ||
| PCT/IB2017/056131 WO2018065923A1 (en) | 2016-10-06 | 2017-10-04 | Bacterial minicells for delivering nucleic acid adjuvants and methods of using the same |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3039010A1 true CA3039010A1 (en) | 2018-04-12 |
Family
ID=61829954
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3039010A Pending CA3039010A1 (en) | 2016-10-06 | 2017-10-04 | Bacterial minicells for delivering nucleic acid adjuvants and methods of using the same |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US11485976B2 (ja) |
| EP (1) | EP3522935A4 (ja) |
| JP (2) | JP7213798B2 (ja) |
| CN (1) | CN110022905B (ja) |
| AU (1) | AU2017339841A1 (ja) |
| CA (1) | CA3039010A1 (ja) |
| EA (1) | EA201990689A1 (ja) |
| IL (1) | IL265855A (ja) |
| MA (1) | MA46469A (ja) |
| SG (1) | SG11201902940RA (ja) |
| WO (1) | WO2018065923A1 (ja) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2963218C (en) * | 2014-10-03 | 2023-10-24 | Engeneic Molecular Delivery Pty Ltd | Enhanced loading of intact, bacterially derived vesicles with small molecule compounds |
| SG11202100507PA (en) * | 2018-07-23 | 2021-02-25 | Engeneic Molecular Delivery Pty Ltd | Compositions comprising bacterially derived minicells and methods of using the same |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8611832D0 (en) | 1986-05-15 | 1986-06-25 | Holland I B | Polypeptide |
| US5037743A (en) | 1988-08-05 | 1991-08-06 | Zymogenetics, Inc. | BAR1 secretion signal |
| WO1995021191A1 (en) | 1994-02-04 | 1995-08-10 | William Ward | Bioluminescent indicator based upon the expression of a gene for a modified green-fluorescent protein |
| AU6762498A (en) | 1997-03-19 | 1998-10-12 | Zymogenetics Inc. | Secreted salivary zsig32 polypeptides |
| RU2248215C2 (ru) | 1999-05-11 | 2005-03-20 | Орто-Макнейл Фармасьютикал, Инк. | Фармакокинетическое и фармакодинамическое моделирование введения эритропоэтина |
| US20030194798A1 (en) | 2001-05-24 | 2003-10-16 | Surber Mark W. | Minicell compositions and methods |
| PT2302063T (pt) | 2001-10-15 | 2016-07-28 | Engeneic Molecular Delivery Pty Ltd | Minicélulas intactas, como vetores para a transferência de adn e terapêutica genética in vitro e in vivo |
| ES2543710T3 (es) * | 2002-04-04 | 2015-08-21 | Zoetis Belgium S.A. | Oligorribonucleótidos inmunoestimulantes que contienen G y U |
| EP2572714A1 (en) * | 2002-12-30 | 2013-03-27 | 3M Innovative Properties Company | Immunostimulatory Combinations |
| US7611885B2 (en) | 2003-06-24 | 2009-11-03 | Engeneic Molecular Delivery Pty, Ltd. | Pharmaceutically compatible method for purifying intact bacterial minicells |
| ES2362881T3 (es) | 2003-12-09 | 2011-07-14 | Engeneic Molecular Delivery Pty Ltd. | Administración génica dirigida a células de mamífero no fagocíticas a través de minicélulas intactas obtenidas de bacterias. |
| RS54149B1 (en) | 2004-02-02 | 2015-12-31 | Engeneic Molecular Delivery Pty Ltd. | COMPOSITIONS AND PROCEDURES IN VITRO AND IN VIVO, TARGETED MEDICINAL RELEASE IN Mammalian cells via intact minicells derived from bacteria |
| US8772013B2 (en) * | 2004-02-02 | 2014-07-08 | Engeneic Molecular Delivery Pty Ltd | Methods for targeted in vitro and in vivo drug delivery to mammalian cells via bacterially derived intact minicells |
| HUE024999T2 (en) | 2004-08-26 | 2016-02-29 | Engeneic Molecular Delivery Pty Ltd | Introducing functional nucleic acids into mammalian cells with bacterial intact minicells |
| HUE033007T2 (en) | 2006-06-23 | 2017-11-28 | Engeneic Molecular Delivery Pty Ltd | Targeted drug, therapeutic nucleic acid and functional nucleic acid delivery to mammalian cells via intact killed bacterial cells |
| SG10201804257RA (en) | 2007-03-30 | 2018-06-28 | Engeneic Molecular Delivery Pty Ltd Au | Bacterially-derived, intact minicells that encompass plasmid-free functional nucleic acid for in vivo delivery to mammalian cells |
| JP6076899B2 (ja) * | 2010-06-25 | 2017-02-08 | イデラ ファーマシューティカルズ インコーポレイテッドＩｄｅｒａ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． | Ｔｏｌｌ様レセプター３の新規アゴニストおよびその使用方法 |
| EP2599866B1 (en) * | 2010-07-28 | 2017-09-06 | National University Corporation Hokkaido University | Novel nucleic acid having adjuvant activity and use thereof |
| AU2012217728B2 (en) * | 2011-02-15 | 2017-04-27 | Vaxiion Therapeutics, Llc | Therapeutic compositions and methods for antibody and Fc-containing targeting molecule-based targeted delivery of bioactive molecules by bacterial minicells |
| AU2014330895B2 (en) * | 2013-10-04 | 2019-08-15 | Engeneic Molecular Delivery Pty Ltd | Combination tumor treatment with drug-loaded, bispecific ligand-targeted minicells and interferon-gamma |
-
2017
- 2017-10-04 EP EP17857944.7A patent/EP3522935A4/en active Pending
- 2017-10-04 SG SG11201902940RA patent/SG11201902940RA/en unknown
- 2017-10-04 JP JP2019518509A patent/JP7213798B2/ja active Active
- 2017-10-04 WO PCT/IB2017/056131 patent/WO2018065923A1/en unknown
- 2017-10-04 CN CN201780073718.5A patent/CN110022905B/zh active Active
- 2017-10-04 US US15/725,008 patent/US11485976B2/en active Active
- 2017-10-04 MA MA046469A patent/MA46469A/fr unknown
- 2017-10-04 CA CA3039010A patent/CA3039010A1/en active Pending
- 2017-10-04 EA EA201990689A patent/EA201990689A1/ru unknown
- 2017-10-04 AU AU2017339841A patent/AU2017339841A1/en active Pending
-
2019
- 2019-04-04 IL IL265855A patent/IL265855A/en unknown
-
2022
- 2022-11-30 JP JP2022190928A patent/JP2023022207A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| JP2023022207A (ja) | 2023-02-14 |
| WO2018065923A1 (en) | 2018-04-12 |
| JP7213798B2 (ja) | 2023-01-27 |
| SG11201902940RA (en) | 2019-05-30 |
| IL265855A (en) | 2019-06-30 |
| JP2019533663A (ja) | 2019-11-21 |
| US11485976B2 (en) | 2022-11-01 |
| US20180100159A1 (en) | 2018-04-12 |
| CN110022905B (zh) | 2024-02-06 |
| CN110022905A (zh) | 2019-07-16 |
| AU2017339841A1 (en) | 2019-05-02 |
| EP3522935A4 (en) | 2020-05-13 |
| EP3522935A1 (en) | 2019-08-14 |
| EA201990689A1 (ru) | 2019-10-31 |
| TW201828994A (zh) | 2018-08-16 |
| MA46469A (fr) | 2019-08-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20210030813A1 (en) | Engineered immunostimulatory bacterial strains and uses thereof | |
| US11168326B2 (en) | Engineered immunostimulatory bacterial strains and uses thereof | |
| US9828601B2 (en) | Compositions for inhibiting checkpoint gene expression and uses thereof | |
| JP4505749B2 (ja) | Ｂｃｌ−２の発現抑制をするオリゴ二本鎖ＲＮＡとそれを含有する医薬組成物 | |
| EP3269811B1 (en) | Nucleic acid having adjuvant activity and use thereof | |
| JP2023022207A (ja) | 核酸アジュバントを送達するための細菌ミニ細胞およびその使用方法 | |
| US10111898B2 (en) | Anti-tumor compositions and methods | |
| JP2023539454A (ja) | 免疫刺激細菌ベースのワクチン、治療薬およびｒｎａデリバリープラットフォーム | |
| WO2010042530A2 (en) | Nlrc5 as a target for immune therapy | |
| JP2022525866A (ja) | 粘膜癌の処置のための、単独の、またはｉ型ｉｆｎインデューサーと組み合わせた、キトサンポリプレックスベースのｉｌ－１２の局部発現 | |
| KR20220020378A (ko) | 종양 치료용 약물 조성물, 키트 및 방법 | |
| TWI840322B (zh) | 用於遞送核酸佐劑之細菌袖珍型細胞及其使用方法 | |
| EA042717B1 (ru) | Композиция для доставки молекулы адъюванта на основе нуклеиновой кислоты | |
| EP3278816A1 (en) | Modified cancer cell lines and uses thereof | |
| US20220168331A1 (en) | PRR-Activating and MicroRNA-Inhibiting Molecules and Methods of Using Same |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20220920 |
|
| EEER | Examination request |
Effective date: 20220920 |
|
| EEER | Examination request |
Effective date: 20220920 |
|
| EEER | Examination request |
Effective date: 20220920 |